{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T02:03:07Z","timestamp":1788832987501,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002657","name":"Istanbul \u00dcniversitesi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002657","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Endometriosis is an estrogen\u2010dependent, chronic inflammatory disease that affects 10% of women during the reproductive ages. Despite the estimated 50% heritability for the condition, only 26% was associated with common genetic variants. Thus, necessity of identifying rare variants for the missing heritability is implicated in the literature. Therefore, our study aimed to identify novel rare genetic variants involved in the pathogenesis of endometriosis utilizing a family of multiple affected members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A family composed of four affected women along with their two unaffected mothers were recruited at a single gynecology and infertility clinic specialized in endometriosis. All patients presented with endometriomas, which was visualized by transvaginal ultrasonography. Two affected individuals had received laparoscopic endometrioma excision and therefore were diagnosed with recurrent disease. One mother had a history of endometrial serous adenocarcinoma (ESC) for which she underwent hysterectomy with bilateral oophorectomy. Three endometriosis cases were whole exome sequenced on Illumina NextSeq 550 platform with an average of 90% coverage. Candidate genes were confirmed by Sanger sequencing and followed\u2010up with family segregation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Novel rare variants were identified in <jats:italic>TNFRSF1B<\/jats:italic> (NM_001066.3: c.1072G&gt;A, p.(Ala358Thr)) and <jats:italic>GEN1<\/jats:italic> (NM_001130009.3: c.1574C&gt;T, p.(Ser525Leu)) as possible genetic causes of endometriosis. A third novel rare variant was identified in <jats:italic>CRABP1<\/jats:italic> (NM_004378.3:c.54G&gt;C, p.(Glu18Asp)) only on the mother with ESC history and her daughters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Novel candidate genetic variants that might contribute to endometriosis were suggested that need replication through independent cohorts or validation by functional studies. The family has also received genetic counseling and that the affected daughters are on clinical follow\u2010up, accordingly.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2312","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T07:29:40Z","timestamp":1701156580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Whole exome sequencing reveals novel candidate variants for endometriosis utilizing multiple affected members in a single family"],"prefix":"10.1002","volume":"12","author":[{"given":"Busra Gizem","family":"Kina","sequence":"first","affiliation":[{"name":"Department of Genetics, Aziz Sancar Institute of Experimental Medicine Istanbul University  Istanbul Turkey"},{"name":"Graduate School of Health Sciences Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-9987","authenticated-orcid":false,"given":"Nura Fitnat","family":"Topbas\u00a0Selcuki","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Istanbul Sisli Hamidiye Etfal Training and Research Hospital University of Health Sciences Turkiye  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar Yalcin","family":"Bahat","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Istanbul Kanuni Sultan Suleyman Training and Research Hospital University of Health Sciences Turkiye  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taner","family":"Usta","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Acibadem Altunizade Hospital Mehmet Ali Aydinlar University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevcan","family":"Aydin","sequence":"additional","affiliation":[{"name":"Department of Genetics, Aziz Sancar Institute of Experimental Medicine Istanbul University  Istanbul Turkey"},{"name":"Graduate School of Health Sciences Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilufer","family":"Rahmioglu","sequence":"additional","affiliation":[{"name":"Oxford Endometriosis Care Centre, Nuffield Department of Women's and Reproductive Health University of Oxford, Women's Centre, John Radcliffe Hospital  Oxford UK"},{"name":"Wellcome Centre for Human Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8233-1839","authenticated-orcid":false,"given":"Feyza Nur","family":"Tuncer","sequence":"additional","affiliation":[{"name":"Department of Genetics, Aziz Sancar Institute of Experimental Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engin","family":"Oral","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Bezmialem Vakif University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"issue":"3","key":"e_1_2_13_3_1","first-page":"1716","article-title":"Whole exome sequencing identifies hemizygous deletions in the UGT2B28 and USP17L2 genes in a three\u2010generation family with endometriosis","volume":"19","author":"Albertsen H. 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